Miltefosine

Miltefosine
Miltefosine
Systematic (IUPAC) name
2-(hexadecoxy-oxido-phosphoryl)oxyethyl-trimethyl-azanium
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat.  ?
Legal status  ?
Routes Oral
Pharmacokinetic data
Bioavailability High
Half-life 6 to 8 days and 31 days [1]
Identifiers
CAS number 58066-85-6 YesY
ATC code L01XX09
PubChem CID 3599
ChemSpider 3473 YesY
UNII 53EY29W7EC N
KEGG D02494 YesY
ChEMBL CHEMBL125 YesY
Chemical data
Formula C21H46NO4P 
Mol. mass 407.568 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Miltefosine (INN, trade names Impavido and Miltex) is a phospholipid drug.

Originally developed as an antineoplastic (and licenced for topical use),[2] it is finding use as an antiprotozoal drug. It can be administered orally and topically.

It acts as an Akt inhibitor.

It is also under investigation as a potential therapy against HIV infection.[3][2]

Contents

Current antiprotozoal and antifungal applications

Leishmania: Miltefosine is registered and used by Zentaris GmbH in India, Colombia and Germany for the treatment of visceral and cutaneous leishmaniasis, and is undergoing clinical trials for this use in several other countries, such as Brazil[4] and Guatemala.[5] Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however a 2005 survey concluded that Miltefosine is the only effective oral treatment for both forms of leishmaniasis.[6]

Investigatory antiprotozoal and antifungal usage

Miltefosine is being investigated by researchers interested in finding treatments for infections which have become resistant to existing drugs. Animal and in-vitro studies suggest it may have broad anti-protozoal and anti-fungal properties:

  • Animal studies suggest miltefosine may also be effective against Trypanosoma cruzi, the parasite responsible for Chagas' disease.[7]
  • An in-vitro study found that Miltefosine is effective against metronidazole-resistant variants of Trichomonas vaginalis, a sexually transmitted protozoal disease.[9]
  • Hexadecyltrimethylammonium bromide, a compound structurally similar to miltefosine, was recently found to exhibit potent in vitro activity against Plasmodium falciparum.[10]

Investigatory usage against HIV infection

Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary human macrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells.[2]

Side effects

The main side effects reported with miltefosine treatment are nausea and vomiting. Miltefosine has exhibited teratogenicity, and should not be administered to pregnant women.

References

  1. ^ Dorlo TP, van Thiel PP, Huitema AD, Keizer RJ, de Vries HJ, Beijnen JH, de Vries PJ (2008). "Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients.". Antimicrob Agents Chemother 52 (8): 2855–60. doi:10.1128/AAC.00014-08. PMC 2493105. PMID 18519729. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2493105. 
  2. ^ a b c Chugh P, Bradel-Tretheway B, Monteiro-Filho CM, et al. (2008). "Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy". Retrovirology 5 (1): 11. doi:10.1186/1742-4690-5-11. PMC 2265748. PMID 18237430. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2265748. 
  3. ^ "Parasitic Drug Shows HIV-Fighting Promise". AIDSmeds.com. 2008-02-01. http://www.aidsmeds.com/articles/hiv_miltefosine_macrophages_1667_13933.shtml. Retrieved 2008-02-02. 
  4. ^ Cristina, Márcia; Pedrosa, Robert (September 2005). "Hospital de Doenças Tropicais testa droga contra calazar" (in Portuguese). Sapiência (Fundação de Amparo à Pesquisa do Estado do Piauí). Archived from the original on 2006-08-22. http://web.archive.org/web/20060822060527/http://www.fapepi.pi.gov.br/sapiencia6/pesquisa3.php. Retrieved 2006-09-01. 
  5. ^ Soto J, Berman J (2006). "Treatment of New World cutaneous leishmaniasis with miltefosine.". Trans R Soc Trop Med Hyg 100: S34. doi:10.1016/j.trstmh.2006.02.022. PMID 16930649. 
  6. ^ Berman, J. (2005). "Clinical status of agents being developed for leishmaniasis". Expert Opinion on Investigational Drugs 14 (11): 1337–1346. doi:10.1517/13543784.14.11.1337. PMID 16255674. 
  7. ^ Saraiva V, Gibaldi D, Previato J, Mendonça-Previato L, Bozza M, Freire-De-Lima C, Heise N (2002). "Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi.". Antimicrob Agents Chemother 46 (11): 3472–7. doi:10.1128/AAC.46.11.3472-3477.2002. PMC 128733. PMID 12384352. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=128733. 
  8. ^ Widmer F, Wright L, Obando D, Handke R, Ganendren R, Ellis D, Sorrell T (2006). "Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis.". Antimicrob Agents Chemother 50 (2): 414–21. doi:10.1128/AAC.50.2.414-421.2006. PMC 1366877. PMID 16436691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1366877. 
  9. ^ Blaha C, Duchêne M, Aspöck H, Walochnik J (2006). "In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis". J. Antimicrob. Chemother. 57 (2): 273–8. doi:10.1093/jac/dki417. PMID 16344287. 
  10. ^ Choubey V, Maity P, Guha M, et al. (February 2007). "Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism". Antimicrob. Agents Chemother. 51 (2): 696–706. doi:10.1128/AAC.00919-06. PMC 1797733. PMID 17145794. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1797733. 

External links

  • Eissa M. M., Bardicy S. E. & Tadros M. (2011). "Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy". Parasites & Vectors 4: 73. doi:10.1186/1756-3305-4-73.

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Look at other dictionaries:

  • miltefosine — noun An antiprotozoal drug, 2 (hexadecoxy oxido phosphoryl)oxyethyl trimethyl azanium, used in oral treatment of leishmaniasis …   Wiktionary

  • miltefosine — mil·tef·o·sine (mil tefґo sēn) a phospholipid derivative that disrupts certain types of cell membranes and is used in treatment of visceral leishmaniasis; administered orally …   Medical dictionary

  • Leishmaniasis — Classification and external resources Cutaneous leishmaniasis in the hand of a Central American adult …   Wikipedia

  • B55 — Leishmaniose Leishmaniose CIM 10 : B55 Les leishmanioses sont des affections cutanées ou viscérales dues à des protozoaires flagellés appartenant au genre Leishmania de la famille des Trypanosomidae et transmises par la piqûre de certaines… …   Wikipédia en Français

  • Leishmaniose — Classification internationale des maladies CIM 10 : B55 La leishmaniose est une maladie chronique à manifestation cutanée et/ou viscérale (on parle de leishmanioses au pluriel) due à des protozoaires flagellés appartenant au genre Leishmania de… …   Wikipédia en Français

  • Miltefosin — Strukturformel Allgemeines Freiname Miltefosin Andere Namen …   Deutsch Wikipedia

  • Visceral leishmaniasis — Classification and external resources Amastigotes in a chorionic villus ICD 10 B …   Wikipedia

  • Kala-Azar — Leishmaniose viscérale Pour les articles homonymes, voir LV. La leishmaniose viscérale (LV), également connue sous le nom de kala azar, ou de fièvre noire, est la forme la plus grave de leishmaniose. Il s agit d une maladie causée par un parasite …   Wikipédia en Français

  • Kala azar — Leishmaniose viscérale Pour les articles homonymes, voir LV. La leishmaniose viscérale (LV), également connue sous le nom de kala azar, ou de fièvre noire, est la forme la plus grave de leishmaniose. Il s agit d une maladie causée par un parasite …   Wikipédia en Français

  • Leishmaniose Viscérale — Pour les articles homonymes, voir LV. La leishmaniose viscérale (LV), également connue sous le nom de kala azar, ou de fièvre noire, est la forme la plus grave de leishmaniose. Il s agit d une maladie causée par un parasite du genre Leishmania .… …   Wikipédia en Français

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